The Hypotensive and Vasodilatory Effects Observed in Rats Exposed to Chiranthodendron pentadactylon Larreat Flowers Can Be Attributed to Cyanidin 3-O-Glucoside.

Chiranthodendron pentadactylon Larreat is a tree native to southeastern Mexico and Guatemala. Its flower is used in Mexican folk medicine to treat a variety of diseases, including conditions of blood pressure. However, scientific information on its usefulness in this pathology is lacking. The present study evaluates the effect of a methanolic extract (ME) from the flower and its active constituents on heart rate (HR) and mean arterial pressure (MAP) in anesthetized rats (MAPHR). The study also analyzed the effects on rat-isolated aortic rings (RIAR) and the rat mesenteric arterial bed (MABR). Active fractions were chromatographed, which led to the isolation of cyanidin 3-O-glucoside (C3G) identified through HPLC. The Chiranthodendron pentadactylon flowers produced hypotensive and vasorelaxant effects associated with C3G. The vasorelaxant effect is a mechanism underlying the synthesis and release of nitric oxide (NO). Neither cholinergic receptors nor prostaglandins are involved. ME and C3G cause cardiovascular depression in anesthetized rats via cholinergic and prostanoid mechanisms. Our research expands the scientific understanding of the flowers on the rat cardiovascular system. This amplifies the appreciation of the flower's ethnomedicine employed to control blood pressure. However, researchers need to conduct toxicity studies to determine the safety of this plant.

Discovering Potential Compounds for Venous Disease Treatment through Virtual Screening and Network Pharmacology Approach.

Peripheral venous hypertension has emerged as a prominent characteristic of venous disease (VD). This disease causes lower limb edema due to impaired blood transport in the veins. The phlebotonic drugs in use showed moderate evidence for reducing edema slightly in the lower legs and little or no difference in the quality of life. To enhance the probability of favorable experimental results, a virtual screening procedure was employed to identify molecules with potential therapeutic activity in VD. Compounds obtained from multiple databases, namely AC Discovery, NuBBE, BIOFACQUIM, and InflamNat, were compared with reference compounds. The examination of structural similarity, targets, and signaling pathways in venous diseases allows for the identification of compounds with potential usefulness in VD. The computational tools employed were rcdk and chemminer from R-Studio and Cytoscape. An extended fingerprint analysis allowed us to obtain 1846 from 41,655 compounds compiled. Only 229 compounds showed pharmacological targets in the PubChem server, of which 84 molecules interacted with the VD network. Because of their descriptors and multi-target capacity, only 18 molecules of 84 were identified as potential candidates for experimental evaluation. We opted to evaluate the berberine compound because of its affordability, and extensive literature support. The experiment showed the proposed activity in an acute venous hypertension model.

Acute morphological changes in guinea-pig ileum myenteric neurons after ischemia in situ with superfusion in vitro.

We evaluated changes involving the myenteric neurons of the guinea pig after different times of ischemia in situ followed by superfusion in vitro. Intestinal ischemia was produced by clamping the superior mesenteric artery and maintaining it for 5, 10, 20, 40, 80, or 160 min. Myenteric plexus-longitudinal muscle preparations from ischemic and non-ischemic portions, obtained from the same guinea pig, were dissected and mounted in organ baths containing Krebs bicarbonate solution at 37 degrees C, gassed with 95% O(2) and 5% CO(2). After 2 h of superfusion, ischemic and non-ischemic strips were removed, immersed in a fixative solution, and processed for light and electron microscopy. We found that ultrastructural neuronal changes, which corresponded with light microscopy findings, developed over time. Some structural changes started after 10 min of ischemia, including cell swelling, chromatin clumping, vacuolization, and disruption of protoplasmic and mitochondrial membranes. Smooth muscle cells changes paralleled those observed in the myenteric neurons, but were evidenced until 40 min of ischemia were completed. These results show that ischemia produces acute time-dependent structural changes in the guinea-pig small intestine, and that affected cells exhibit primarily morphological changes characteristic of necrosis.

Exploratory studies of some Mexican medicinal plants: Cardiovascular effects in rats with and without hypertension.

BACKGROUND: Papaveraceae Argemone mexicana L., Burseraceae Bursera simaruba (L.) Sarg., Acanthaceae Justicia spicigera Schltdl. and Selaginellaceae Selaginella lepidophylla (Hook. & Grev.) Spring., have been used in Mexican traditional medicine to treat hypertension. The objective of this study was to further characterize the cardiovascular effects of the methanol extracts of such plants. METHODS: The medicinal plants were collected and taxonomically identified; the methanol extract of each explored plant were administrated to conscious and unconscious male Wistar rats with and without glucose-induced hypertension. The blood pressure (BP) and heart rate (HR) were evaluated before and after the extract administration. Vascular reactivity experiments were conducted in rat aortic rings obtained from rats with and without sugar-induced hypertension, a model widely used to study such effects with cardiovascular agents. RESULTS: After oral administration in normotensive conscious rats all tested extracts decreased the HR, such effect was only observed in hypertensive conscious rats after the administration of B. simaruba; only A. mexicana and B. simaruba decreased the BP after oral administration. All extracts administrated by intravenous injection diminished the mean arterial pressure. Dose-response curves to cumulative concentrations of all the extracts promote vascular relaxation in precontracted aortas from rats with and without sugar-induced hypertension. CONCLUSIONS: The present study indicated that B. simaruba is worthy of further investigation as a potential phytotherapeutic agent for treating hypertension.

Altered responsiveness of the guinea-pig isolated ileum to smooth muscle stimulants and to electrical stimulation after in situ ischemia.

1. We evaluated changes in contractility of the guinea-pig isolated ileum, using intact segments and myenteric plexus-longitudinal muscle (MPLM) preparations, after several times (5-160 min) of ischemia in situ. 2. Intestinal ischemia was produced by clamping the superior mesenteric artery. Ischemic and nonischemic segments, obtained from the same guinea-pig, were mounted in organ baths containing Krebs-bicarbonate (K-B) solution, maintained at 37 degrees C and gassed with 95% O2/5% CO2. The preparations were allowed to equilibrate for 60 min under continuous superfusion of warm K-B solution and then electrically stimulated at 40 V (0.3 Hz, 3.0 ms). Thereafter, complete noncumulative concentration-response curves were constructed for acetylcholine (ACh), histamine (HIS), potassium chloride (KCl), and barium chloride (BaCl2). Mean Emax (maximal response) values were calculated for each drug. 3. Our study shows that alterations of chemically and electrically evoked contractions are dependent on ischemic periods. It also demonstrates that contractile responses of ischemic tissues to neurogenic stimulation decreases earlier and to a significantly greater extent than the non-nerve mediated responses of the intestinal smooth muscle. Contractile responses to smooth muscle stimulants were all similarly affected by ischemia. Electron microscopy images indicated necrotic neuronal death. The decrease in reactivity of ischemic tissues to electrical stimulation was ameliorated by dexrazoxane, an antioxidant agent. 4. We consider the guinea-pig isolated ileum as a useful model system to study the processes involved in neuronal ischemia, and we propose that the reduction in maximal responses to electrical stimulation is a useful parameter to study neuroprotection.

A simplified procedure for the quantitative measurement of neurological deficits after forebrain ischemia in mice.

This study describes a comprehensive method to assess neurological deficits after brain ischemia produced by sequential common carotid artery sectioning (SCAS) in aged mice, and a scale to determine the degree of functional incapacity of ischemic animals. The method involves an initial phase of undisturbed observation and a later manipulative phase during which each animal is subjected to a sequence of very simple manipulations. Sham-operated animals demonstrated 96% survival throughout the study period (72 h), whereas the 24, 48 and 72 h survival rates of SCAS-mice were 48, 38 and 36%, respectively. In the surviving SCAS-mice, we detected a total of 23 neurological alterations throughout the observation period (72 h); the most frequent alterations were: motor incoordination, abnormal body position, hypomobility, decreased body tone and muscular strength, tremor, hunched back, passivity, forelimb flexion and ataxic gait. Based on these alterations, we used a global scale that comprises 10 progressive grades beyond 0 (normal), extending to status 10 (death due to SCAS), with higher scores indicating greater deficit. The median neurological scores for sham-operated animals were 1.36, 1.48 and 1.32 at 24, 48 and 72 h, respectively, whereas total neurological scores in SCAS-mice of 6.1, 6.8 and 7.4, at 24, 48 and 72 h, respectively, were substantially greater than those observed in sham-operated animals. The simplicity of the procedure, herein described, to measure the functional neurological condition of ischemic animals, and the remarkable level of functional impairment produced by SCAS offer the possiblity to test the efficacy of putative stroke therapies and to monitor progress of deficits over time in groups of animals.